방사선의학 웹진

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Abstract

BACKGROUND:
We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-freesurvival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial.

METHODS:
TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided.

RESULTS:
With a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively ( P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to multicollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4.

CONCLUSIONS:
Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level.

Author information

Fokas E1, Ströbel P1, Fietkau R1, Ghadimi M1, Liersch T1, Grabenbauer GG1, Hartmann A1, Kaufmann M1, Sauer R1, Graeven U1, Hoffmanns H1, Raab HR1, Hothorn T1, Wittekind C1, Rödel C1; German Rectal Cancer Study Group.

1 

Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany; Institute of Pathology and Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany; Department of Radiation Therapy and Institute of Pathology, University of Erlangen-Nürnberg, Nürnberg, Germany; Department of Radiation Oncology and Radiotherapy, DiaCura and Klinikum Coburg, Coburg, Germany; Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland; Department of Hematology/Oncology and Gastroenterology and Department of Radiation Oncology, Kliniken Maria Hilf GmbH Mönchengladbach, Mönchengladbach, Germany; Department of General and Visceral Surgery, University of Oldenburg, Oldenburg, Germany; Institute of Pathology, University of Leipzig, Leipzig, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), partner site: Frankfurt/Mainz, Heidelberg, Germany.